The Neurocritic

Wednesday, February 29, 2012

A 34-year-old physical therapist, Kristen, who suffered a stroke in 2008 relates her journey and rebuilds her life with Aphasia. Aphasia is a language disorder that affects the language center of the brain and is caused by stroke, brain surgery or other traumatic brain injuries. Kristen's positive attitude has taken her down a new path for helping others. With the help of further intense speech therapy Kristen hopes to inspire other with Aphasia.

Kristen's stroke has likely affected her left frontal lobe. She has speech output problems but speaks fluently enough to not be characterized with a classic Broca's aphasia. She has some motor weakness on the right (contralateral) side of her body, but with adaptive technology is able to drive. She continues to go to physical therapy and has a positive outlook and an active life.

Tuesday, February 28, 2012

Now in its third year, the Neuro Film Festival is a contest by the American Academy of Neurology Foundation to help raise awareness about why more research is needed to cure brain diseases, such as Alzheimer's disease, stroke, autism, Parkinson's disease and multiple sclerosis.

Public voting will close on March 8, 2012, with the winner of the "Fan Favorite" award receiving a certificate and recognition at the 2012 Neuro Film Festival on April 22, 2012, in conjunction with the American Academy of Neurology's 64th Annual Meeting, the world's largest meeting of neurologists with 10,000 attendees.

Entries closed on January 31, but the introductory video below explains the purpose of the contest: "to raise awareness through film and video about brain disorders and the need to support research into preventions, treatments and cures."

Saturday, February 18, 2012

The artwork of M.C. Escher is famous for its visual trickery. The human visual system tries to project the two dimensional image onto a three dimensional scene, but the perspective is contradictory: it cannot exist in the real world. These impossible constructions violate the laws of geometry and fascinate consumers of t-shirts, posters, and Apple products.

How does the brain represent these illusory staircases and towers? While a fascinating topic of study in the field of object perception (Levy et al., 2004), Escher prints can make for overly complicated stimuli in neuroimaging experiments. Simpler 2D figures, such as the impossible objects drawn by Swedish artist Oscar Reutersvärd, have been used in fMRI experiments (Soldan et al., 2008).

An extensive collection of 810 impossible objects is available from Impossible World, which is a fantastic resource1 maintained by Vlad Alexeev.

A set of occipital, parietal, and temporal brain regions decreased their activation across presentations, including bilateral middle occipital gyrus, left precuneus, right supramarginal gyrus, as well as some frontal and thalamic areas, such as right inferior frontal gyrus, left cingulate gyrus, and right thalamus.

However, no such relationship was observed for impossible objects.

The previous studies focused on varieties of repetition priming and whether there is a "structural description system" that facilitates the identification of perceptually coherent objects. A recently published article was specifically interested in the neural basis of impossible figures and how they are represented in the visual cortex (Wu et al., 2012). The stimuli were impossible and possible exemplars of the two-pronged trident (Fig. 1 below), shown at four different angles.

Fig. 1 (Wu et al., 2012).Examples of stimulus figures used in impossible condition and possible condition. (a) Is an impossible figure and (b) is a possible figure [that] resembles the former.

The paper started by reviewing the basic neuroanatomy of the visual system and its division into dorsal ("where") and ventral ("what") visual streams. Objects are primarily represented in the ventral stream, and the lateral occipital complex (LOC) is one area that seems to be specialized for object recognition. The authors predicted that impossible objects would be difficult for the LOC to process; therefore, additional regions would be recruited:

In the present study, we thought that the 3D structures of impossible figures might be difficult to be represented by object-selective regions (such as the LOC), and the impossible perceptions might be derived from detecting the contradiction in interpretation of the 3D structure. Therefore, we postulated that both the brain regions in the dorsal visual pathway, such as the SPC [superior parietal cortex] related to the perceptual ambiguities resolving and perceptual content modifying, and the brain areas related to the object-selective regions in the ventral pathway would be involved in the impossible figures processing.

Nineteen participants performed the possible/impossible object decision task (30 trials of each condition) while their brains were scanned. Four participants showed repetition priming in the task (first 15 trials of each condition slower than the last 15) and were excluded. The remaining subjects did not show priming.3 Personally, I would have used 30 unique possible and impossible figures to avoid priming effects entirely.

What were the results? As predicted, regions in both dorsal and ventral visual streams showed greater activation for impossible than for possible figures: right superior parietal in the former and right fusiform and inferior temporal gyri in the latter.

The right SPG in the dorsal visual pathway might be related to spatial information processing and the right LOC (FG and ITG) in the ventral visual pathway (the object-selective regions) might be related to the representation of the impossible 3D structure. Therefore, our results indicated that the impossible 3D structure might be difficult to be represented by human visual system, and the impossible perception might be derived from the detecting and resolving the contradiction in the subjects’ interpretations according to different perceptions triggered by 3D cues.

There were no brain regions that showed greater activation for possible objects.The authors suggested that their ventral stream regions are part of LOC, although this is debatable. In the original study of Malach et al. (1995), LOC is posterior to the inferior temporal focus here, but Grill-Spector et al. (2001) state that:

...the entire region, beginning in lateral occipital cortex and extending anteriorly and ventrally into posterior temporal regions, responds more strongly to intact objects with clear shape interpretations than to control stimuli that do not depict clear shapes.

LOC doesn't seem to differentiate between familiar objects and unfamiliar objects with clear 3D interpretations (e.g. Henry Moore sculptures). At any rate, what's interesting here is that LOC was more active for impossible objects, suggesting that "the 3D spatially impossible structure could, [with difficulty], be represented by the visual system." And that, along with greater activity in the right superior parietal cortex, is how the brain processes impossible objects.

Is Intensive Sleep Retraining (ISR) a new overnight treatment for chronic insomnia (Harris et al., 2012)? ISR is conducted in one 25 hr session at a sleep lab, where the insomniac sleeps a maximum of 3 min every 30 min for a period of 25 hrs. Instant cure! (supposedly). The basic idea is that the person will learn they can fall asleep fairly quickly and easily, and this will translate directly to real life sleeping patterns.

...a novel insomnia treatment that while radical in procedure is grounded in learning theory, a long-established conceptual framework for understanding insomnia. ISR combines two familiar components of sleep research—sleep deprivation and the polysomnographic recording of sleep onset—to yield an entirely new therapeutic procedure: repeated practice in falling asleep quickly. Massed practice in achieving sleep is here shown to possess a therapeutic value rivaling that of stimulus control therapy (SCT), that mainstay of behavioral sleep medicine, as well as offering a possible additive effect when administered in conjunction with SCT.

ISR employs sleep laboratory technology to measure the speed of sleep onset, limit the duration of sleep, and allow immediate feedback to subjects as to whether objectively recorded sleep has occurred. It typically provides dozens of successful entries to sleep over the course of a single night and day. Then it is over, handing off responsibility for good sleep management to sleep hygiene recommendations.

...reduce the anxiety or conditioned arousal individuals may feel when attempting to go to bed. Specifically, a set of instructions designed to reassociate the bed/bedroom with sleep and to re-establish a consistent sleep schedule are implimented. These include: 1) Going to bed only when sleepy; 2) Getting out of bed when unable to sleep; 3) Using the bed/bedroom only for sleep and sex (i.e., no reading, watching TV, etc); 4) Arising at the same time every morning; and 5) Avoiding naps.

One question, then, is whether ISR is better than SCT, an accepted behavioral therapy for insomnia. Eighty participants in the study of Harris et al. were randomized into one of four groups: (1) ISR + sleep hygeine instruction (SH); (2) SCT + SH; (3) ISR + SCT; (4) SH alone, which served as the control condition. All participants kept a sleep diary, answered questionnaires, and wore an actigraph to measure motor activity. Those in the ISR groups slept no more than 5 hrs the night before they came to the lab.

The highly intrusive ISR procedure involved arriving at 21:00.

Following an explanation, the signing of an informed consent form, electrode application, and a quiet settling period, treatment began at 22:30. Treatment trials were conducted every half hour, finishing after 23:00 on night 2. Thereby, the ISR treatment routine allowed a series of 50 half-hourly sleep onset opportunities. ... Within each treatment trial, the opportunity for sleep onset was limited to a 20-min period, with the trial stopping if sleep onset had not occurred by this time. For those trials in which sleep was initiated, 3 consecutive minutes of sleep were permitted, prior to being awoken [the method of awakening was not described]. Upon awakening, treatment participants first rated their perception of whether sleep onset had occurred (on a Likert scale of 1 “No, definitely not” to 7 “Yes, definitely”). Following this response, participants were provided with information as to whether sleep onset had or had not occurred.

Then they got out of bed to read or watch DVDs. After 10 trials of this nonsense, people were falling asleep in 5 min or less.

Ultimately, did this punitive procedure work? Yes. But it wasn't significantly better than SCT for most of the subjective sleep measures used. All three active treatment conditions produced improvements in self-reported duration and efficiency of sleep, relative to the SH control. Of the 16 or so analyses at 2 of 7 selected time points (which did not seem to be corrected for multiple comparisons), there were some instances where ISR or the combined ISR + SCT treatment was better than stimulus control therapy (see below), but nothing earth shattering.

In another graph (Fig. 5 - Mean sleep diary wake time after sleep onset), the SCT groups were superior to ISR at Week 1 and Post-Treatment.

What about the objective sleep measures obtained by actigraphy?

The actigraphy data failed to support significant changes in sleep, despite using an adjusted manual scoring method and a sensitivity setting in the scoring algorithm that calibrated actigraphy TST [total sleep time] to PSG [polysomnography] TST. Actigraphy has similarly failed to mirror subjective sleep changes in other treatment studies in insomnia, and objective measures (i.e., EEG) fail to replicate the extent of subjective sleep changes in clinical insomnia treatment studies.

The authors concluded that actigraphy is useless and that subjective sleep report is the only thing that matters (basically).

So what's next? Intensive Sleep Retraining is costly and available only from highly specialized centers.1 But the possibility of self-administered ISR is on the horizon, using portable EEG headsets, actigraphs, and vibrating alarms. Is there an app for that?

Footnote

1I'm not sure that it's even being offered as a clinical treatment. The RCT was conducted in Australia.

Saturday, February 11, 2012

Try some of these remedies recommended by the finest scientific and medical journals of the day.

As early as the 1880s, hydrotherapy in the form of continuous baths, showers, and wraps was used to treat patients at St. Elizabeths Hospital in Washington, DC.

Writing in the British Medical Journal, Campbell (1885) advocated Warm Douching of the Head and Neck in the Insomnia of Continued or Eruptive Fevers.

"...I wish to point out what I consider a most pleasant and soothing method of employing a douche, especially indicated in sleeplessness, and not contraindicated by cardiac debility; the proceeding is neither novel, difficult, nor disagreeable, and is productive of the best results if efficiently performed.

The patient's shoulders having been wrapped in a sheet or blanket, and his ears plugged with cotton-wool, his head is supported over the edge of the bed (a suitable vessel being placed underneath to receive the water), whilst a gentle stream of warm water from the rose-spout of an ordinary watering-pot is directed over the head and neck. The watering-pot should be held at least eighteen inches above the level of the patient's head, and the douching may be kept up for three or four minutes; the head should then be lightly dried with a towel, and the patient lifted into his ordinary position in bed. As a rule, sleep is produced within a short time."

"INSOMNIA, whether observed as a diseased condition unassociated with any other complaint or as an accompanying symptom of neurasthenia, is sufficiently often met with to warrant me in presenting to the members of this Society a short resume of my past season's work. Insomnia of itself will quickly produce this neurasthenic state, with its long list of vague nervous symptoms, and the physician is sooner or later forced to look for some form of treatment which will combat the two diseases. Most of us know how unreliable drugs are under such circumstances, first because of the uncertainty of securing a definite result, and, second, on account of the great risk run by the patient that he may contract some bad drug-habit, whereby sleep is secured at the time, but the subsequent awakening brings with it the startling realization that he is the victim of one of the enslaving drugs, to escape which he must battle harder than ever man did against the evils resulting from loss of sleep."

Although also considered a treatment for neurasthenia (a 19th c. term for a type of anxiety or nervous exhaustion brought about by overwork), Hance's form of hydrotherapy was less malevolent than prolonged shower-baths for hospitalized psychiatric patients, especially those advocated by Mr. Charles Snape. Dr. Hance explained:

"In my treatment of these cases the temperature of the water is carefully regulated, so that all shock is avoided, and therein lies the secret of the success of the treatment of those who are suffering from neurasthenia or insomnia. If the temperature of the water is such as to shock them they will refuse further treatment."

A particularly interesting case study was that of a woman in her 30s who held an important position that required demanding intellectual work, which was probably unusual at the time.

CASE I.-Female, single, aged thirty-three years; United States. Insomnia alone. Occupies a position of great responsibility, requiring much mental labor and executive ability. For several months past had been sleeping less and less, until two or three hours was the limit of each night's rest. From lack of sleep was physically weak and in a general run-down condition. Physical examination of all organs and functions healthy. No symptoms of neurasthenia.

January 11, 1899. Treatment: Hot-air bath to perspiration. Needle spray, general fan douche, jet douche along spine, followed by general static electrization (positive), with local breeze along the spine. Effect of treatment felt after the third bath, sleeping longer and awakening in the morning more refreshed and stronger.

After twelve treatments, sleeping six hours nightly.

She had a relapse on Jan 27th and received additional treatments. Unfortunately, she had to stop working but later reported the cure had been lasting. Perhaps she could have just quit her job without needing hydrotherapy treatments. Wouldn't most of us sleep better without a very stressful job?

Modern hydrotherapy for the contemporary neurasthenic

Let's return to the classic insomnia treatments now. In an editorial in Science (1889), we learn about:

THE FOOD TREATMENT FOR INSOMNIA. --Dr. Eggleston says, in the journal of the American Medical Association, that most students and women who are troubled with insomnia are dyspeptic, and he has found it easy to successfully treat such cases without medicine. They are instructed to eat before going to bed, having put aside work entirely at least an hour before. If they are not hungry, they should simply be instructed to eat; and if they are hungry, they should eat whatever they want. A glass of milk and a biscuit is sometimes all that can be taken at first, or mashed potato buttered. In a short time the night appetite will grow, and the appetite will then need no particular directions. If possible, the night meal should be taken in another room than the sleeping apartment, and for men in the city it will be found advantageous to go out to a restaurant. The idea of going out for something to eat, and having to wait a short time for it, will excite the appetite. Before eating, however, a bath should be taken, preferably cold or cool, which should be given with a sponge or stiff brush, and the body thoroughly rubbed off with a coarse towel afterward. The bath need not be more than five minutes in duration. After the bathing and rubbing, or after eating, a moderate amount of exercise should be taken. For this a few minutes with Indian clubs or dumb-bells is sufficient. Further than this, the patient should go to bed at the same hour every night, and arise at the same hour every morning. There is a popular superstition that grown people should not eat immediately before going to sleep; that it will give them indigestion or nightmare, or both. Dr. Eggleston cannot see why adults should be so very different in this respect from babies.

"You remember the 90s, when everyone was pickling their own vegetables and brewing their own beer? People were growing out their mutton chops and waxing their handlebar mustaches?" It's the Dream of the 1890s in Portland!

Not everyone thinks this dissociative anesthetic/club drug/animal tranquilizer is a great antidepressant. The Neurocritic covered both sides of the story in Ketamine for Depression: Yay or Neigh? as well as a questionable treatment regimen in Chronic Ketamine for Depression: An Unethical Case Study? On a mechanistic level, the mTOR (mammalian target of rapamycin) protein kinase pathway, which is rapidly activated by ketamine, may have its ups and downs. Although activation of mTOR leads to the beneficial effect of increased synaptogenesis in the medial prefrontal cortex (Li et al., 2010), it can also cause accelerated tumor growth, as recently noted by Yang et al., 2011 ("Be prudent of ketamine in treating resistant depression in patients with cancer").

What if you were depressed 10 yrs ago, tried ketamine but didn't know it was supposed to instantly "cure" your depression, and then ended up merely frightened by the K-hole and not better at all? Has that happened to anyone? The anti-ketamine bandwagon is being led by Gawker and its stable of experienced ketamine users:

Neuropsychiatric researchers say that although traditional antidepressants can take weeks to work, depressed patients who are given BANANAS 'PAUSE BUTTON ON YOUR BRAIN' K-HOLE-INDUCING CLUB DRUG KETAMINE A.K.A. SPECIAL K feel relief from their depression "almost instantly." But could huge shots of heroin combined with a baseball bat to the head be equally effective? Ketamine-receiving patients say [just stares at the wall].

The '90s were a lot of fun the first time around, and there were tons of great things about the decade. We even did a lot of wonderful, powerful, mind-altering substances... K was not one of them. K was a stupid mistake. Even a bigger mistake than Fat Boy Slim, P.L.U.R., and a strange affection for Ring Pops at the age of 20. It was one of the few things I look back on and think, "Man, that was really, really dumb. Why did we ever do that?" If the '90s are going to come back, take this lesson from someone who really enjoyed the first time around—leave the K for the cats.

Finally, I just have to say one thing about this clinical trial on Ketamine For Suicidal Ideation at Mount Sinai. The only primary and secondary outcome measures are at 24 hours post infusion? Really?? You're not following up the patients to see if they're still suicidal a week later, let's say? Is that so difficult?

A hallmark of the individual is the cultivation of personal interests, but for some people, their intellectual pursuits might actually be genetically predetermined. Survey results published by Princeton University researchers in the journal PLoS ONE suggest that a family history of psychiatric conditions such as autism and depression could influence the subjects a person finds engaging.

But the basic premise of asking 18 yr olds for valid psychiatric diagnoses of family members might be flawed, you say? Neuroskeptic posted on this paper, but not skeptically enough, in my view. I would go directly to this comment by Professor Keith R Laws:

Obviously there are a few issues with such studies:1) the ability of individuals to report accrurately - it seems for example that they viewed propsopagnosia as a memory disorder - so they are not identifying at all accurately (at least for some conditions)2) there seem to be strong oddities in the incidence rates e.g. schizophrenia3) in the latter case, there may be a strong social desirability effect4) indeed, in relation to desirability, such individuals may be more prone to endorse stereotypes (of autism-geek etc)5) comorbidities were not apparently evaluated e.g. about a third of all people with autism have a comorbid disorder; similarly with other disorders esp things such as OCD (with sz etc)

And it's really stretching it to say anything at all about genetics from a survey (Campbell & Wang, 2012):

Our results suggest that shared genetic (and perhaps environmental) factors may both predispose for heritable neuropsychiatric disorders and influence the development of intellectual interests.

But, now, research that analyzed more than 100 imaging studies concludes that Wernicke's area is in the wrong location.

The site [not so] newly identified is about 3 centimeters closer to the front of the brain and on the other side of auditory cortex — miles away in terms of brain architecture and function.

The finding, published online this week in the Early Edition of the Proceedings of the National Academy of Sciences (PNAS), means that ‘textbooks will now have to be rewritten,’ says the study's senior author, Josef Rauschecker, Ph.D., a professor in the department of neuroscience at Georgetown University Medical Center (GUMC).

‘We gave old theories that have long hung - a knockout punch,’ says Rauschecker...

‘If you Google 'language organization in the brain,' probably every cartoon illustration out there is wrong,’ says lead author Iain DeWitt, a Ph.D. candidate in Georgetown's Interdisciplinary Program in Neuroscience.

About Me

Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.